Perioperative PET/CT lymphoscintigraphy and fluorescent real-time imaging for sentinel lymph node mapping in early staged colon cancer.

PURPOSE: Using current optical imaging techniques and gamma imaging modalities, perioperative sentinel lymph node (SLN) identification in colon cancer can be difficult when the SLN is located near the primary tumour or beneath a thick layer of (fat) tissue. Sentinel lymph node mapping using PET/CT lymphoscintigraphy combined with real-time visualization of the SLN using near-infrared imaging has shown promising results in several types of cancer and may facilitate the successful identification of the number and location of the SLN in early colon cancer. METHODS: Clinical feasibility of PET/CT lymphoscintigraphy using preoperative endoscopically injected [89Zr]Zr-Nanocoll and intraoperative injection of the near-infrared (NIR) tracer Indocyanine Green (ICG) was evaluated in ten early colon cancer patients. Three preoperative PET/CT scans and an additional ex vivo scan of the specimen were performed after submucosal injection of [89Zr]Zr-Nanocoll. All SLNs and other lymph nodes underwent extensive pathological examination for metastases. A histopathological proven lymph node visible at preoperative PET/CT and identified at PET/CT of the specimen was defined as SLN. RESULTS: A total of 27 SLNs were harvested in seven out of eight patients with successful injection of both tracers. In one patient no SLNs were assigned preoperatively. In two patients injection of [89Zr]Zr-Nanocoll failed due to incorrect needle positioning. Twenty-one (78%) SLNs were found intraoperatively using NIR-imaging. Eleven of the 27 (41%) SLNs were located near the primary tumour (< 2 cm). Those six SLNs not found intraoperatively with NIR-imaging were all located close to the tumour. In all seven patients at least one SLN could be assigned at preoperative imaging 24 h after tracer administration. One SLN contained metastases detected by immunohistochemistry. No metastases were found in the non-SLNs. CONCLUSIONS: This study shows the potential of preoperative PET/CT lymphoscintigraphy to inform the surgeon about the number and location of SLNs in patients with early colon cancer. The additional use of NIR-imaging allows for intraoperative identification of these SLNs which are invisible with conventional white light imaging. Further research is necessary to improve and simplify the technique. We recommend perioperative SLN identification using a preoperative lymphoscintigraphy scan just before surgery approximately 24 h after injection. Additionally a postoperative scan of the specimen combined with intraoperative real-time NIR-imaging should be performed.

PGAT: a multistrain analysis resource for microbial genomes.

MOTIVATION: The Prokaryotic-genome Analysis Tool (PGAT) is a web-based database application for comparing gene content and sequence across multiple microbial genomes facilitating the discovery of genetic differences that may explain observed phenotypes. PGAT supports database queries to identify genes that are present or absent in user-selected genomes, comparison of sequence polymorphisms in sets of orthologous genes, multigenome display of regions surrounding a query gene, comparison of the distribution of genes in metabolic pathways and manual community annotation. AVAILABILITY AND IMPLEMENTATION: The PGAT website may be accessed at http://nwrce.org/pgat. CONTACT: mbrittna@uw.edu.

Real-time diagnostic accuracy of blue light imaging, linked color imaging and white-light endoscopy for colorectal polyp characterization.

Background and study aims Fujifilm has developed a novel ELUXEO 7000 endoscope system that employs light-emitting diodes (LEDs) at four different wavelengths as light sources that enable blue light imaging (BLI), linked color imaging (LCI), and high-definition white-light endoscopy (HD-WLE). The aim of this study was to address the diagnostic accuracy of real-time polyp characterization using BLI, LCI and HD-WLE (ELUXEO 7000 endoscopy system). Patients methods This is a prespecified post-hoc analysis of a prospective study in which 22 experienced endoscopists (> 2,000 colonoscopies) from eight international centers participated. Using a combination of BLI, LCI, and HD-WLE, lesions were endoscopically characterized including a high- or low-confidence statement. Per protocol, digital images were created from all three imaging modalities. Histopathology was the reference standard. Endoscopists were familiar with polyp characterization, but did not take dedicated training for purposes of this study. Results Overall, 341 lesions were detected in 332 patients. Of the lesions, 269 histologically confirmed polyps with an optical diagnosis were included for analysis (165 adenomas, 27 sessile serrated lesions, and 77 hyperplastic polyps). Overall, polyp characterization was performed with high confidence in 82.9 %. The overall accuracy for polyp characterization was 75.1 % (95 % confidence interval [CI] 69.5-80.1 %), compared with an accuracy of 78.0 % (95 % CI 72.0-83.2 %) for high confidence assignments. The accuracy for endoscopic characterization for diminutive polyps was 74.7 % (95 %CI 68.4-80.3 %), compared with an accuracy of 78.2 % (95 % CI 71.4-84.0 %) for high-confidence assignments. Conclusions The diagnostic accuracy of BLI, LCI, and HD-WLE by experienced endoscopist for real-time polyp characterization seems limited (NCT03344289).

Childhood brain tumours due to germline bi-allelic mismatch repair gene mutations.

Childhood brain tumours may be due to germline bi-allelic mismatch repair (MMR) gene mutations in MLH1, MSH2, MSH6 or PMS2. These mutations can also lead to colorectal neoplasia and haematological malignancies. Here, we review this syndrome and present siblings with early-onset rectal adenoma and papillary glioneural brain tumour, respectively, due to novel germline bi-allelic PMS2 mutations. Identification of MMR protein defects can lead to early diagnosis of this condition. In addition, assays for these defects may help to classify brain tumours for research protocols aimed at targeted therapies.

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial.

BACKGROUND: Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life. METHODS/DESIGN: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide. DISCUSSION: The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

Disruption of the developmentally regulated Rev3l gene causes embryonic lethality.

The REV3 gene encodes the catalytic subunit of DNA polymerase (pol) zeta, which can replicate past certain types of DNA lesions [1]. Saccharomyces cerevisiae rev3 mutants are viable and have lower rates of spontaneous and DNA-damage-induced mutagenesis [2]. Reduction in the level of Rev31, the presumed catalytic subunit of mammalian pol zeta, decreased damage-induced mutagenesis in human cell lines [3]. To study the function of mammalian Rev31, we inactivated the gene in mice. Two exons containing conserved DNA polymerase motifs were replaced by a cassette encoding G418 resistance and beta-galactosidase, under the control of the Rev3l promoter. Surprisingly, disruption of Rev3l caused mid-gestation embryonic lethality, with the frequency of Rev3l(-/-) embryos declining markedly between 9.5 and 12.5 days post coitum (dpc). Rev3l(-/-) embryos were smaller than their heterozygous littermates and showed retarded development. Tissues in many areas were disorganised, with significantly reduced cell density. Rev3l expression, traced by beta-galactosidase staining, was first detected during early somitogenesis and gradually expanded to other tissues of mesodermal origin, including extraembryonic membranes. Embryonic death coincided with the period of more widely distributed Rev3l expression. The data demonstrate an essential function for murine Rev31 and suggest that bypass of specific types of DNAlesions by pol zeta is essential for cell viability during embryonic development in mammals.

[Double-balloon enteroscopy for the diagnosis and treatment of patients with unexplained gastrointestinal blood loss]. / Dubbeleballon-enteroscopie bij de diagnostiek en de behandeling van patiënten met onverklaard gastro-intestinaal bloedverlies.

In 3 patients, 2 women aged 56 and 57 and a 65-year-old man, who presented with overt and occult gastrointestinal bleeding, no focus of the bleeding could be found during gastroscopy and colonoscopy. The patients were then examined and treated by double-balloon enteroscopy (DBE). DBE is a relatively new endoscopic technique that allows high-resolution visualisation of the entire small intestine with full endoscopic instrumentation. The 56-year-old woman had coeliac disease and an enteropathy-associated T-cell lymphoma with stenoses over approximately 150 cm of bowel length. She was given chemotherapy and responded well. The 57-year-old woman suffered from Rendu-Osler-Weber syndrome with multiple angiodysplasias in the small intestine. She was treated 5 times with argon plasma coagulation during DBE, for more than 40 angiodysplasias, and thereafter no longer needed blood transfusions. The 65-year-old man had a history of recurrent melanoma. During DBE, multiple metastases of a melanoma in the small intestine were found and tattooed. The tumours were later surgically excised, with no further metastases in the following 2 years. DBE has proven to be a good diagnostic and therapeutic tool in the management of small intestinal diseases.

[Occult gastrointestinal bleeding due to a Dieulafoy lesion in the terminal ileum]. / Occult gastro-intestinaal bloedverlies door een laesie van Dieulafoy in het terminale ileum.

A 50-year-old man awaiting liver transplantation for primary sclerosing cholangitis developed iron-deficiency anaemia. Repeated occult gastrointestinal bleeding led to an increasing need for blood transfusions. After multiple oesophagogastroduodenoscopies and colonoscopies, videocapsule endoscopy finally demonstrated a polyp-like lesion in the terminal ileum. The lesion had not been detected despite two attempts (oral and anal) at double-balloon enteroscopy and even a peroperative enteroscopy. Only during a second laparotomy, again involving peroperative enteroscopy, a small red lesion was detected and resected 80 cm proximal to the ileocecal valve (Bauhin's valve). Histology revealed a Dieulafoy lesion. Four months later, after normalisation and stabilisation of his haemoglobin level, the patient received a successful liver transplant. If the cause of occult gastrointestinal bleeding in a patient remains unclear despite regular endoscopic procedures, new techniques like videocapsule endoscopy and double-balloon enteroscopy may contribute to identifying the cause. This may lead to an exceptional finding such as a Dieulafoy lesion in the distal ileum.

Milestone in gastrointestinal endoscopy: double-balloon enteroscopy of the small bowel.

The small bowel (SB) has been largely bypassed by flexible endoscopy because of inaccessibility. Push enteroscopy is now in the past, with recent innovations now making visualization of the SB possible. Wireless capsule endoscopy (CE) and double-balloon endoscopy (DBE) have been introduced. In this review, we focus on the diagnostic and therapeutic modalities of DBE, which may be a suitable replacement for push enteroscopy, preoperative endoscopy and to some extent of SB fall-through and CT scan. DBE is a new method of endoscopy developed and described by Yamamoto et al. in Jichi, Japan, in cooperation with Fujinon. Introduced to the market in 2003, it is possible with this endoscope to observe the entire SB in steps of 20-40 cm. Measuring the depth of insertion is also possible. Obscure gastrointestinal bleeding can be explained and treated in the majority of cases. Biopsy sampling, hemostasis, polypectomy, dilatation and tattoo are possible in the SB. Guidelines for FAB and Peutz-Jeghers syndrome will probably be reviewed in the next few years. The safety and efficacy of DBE have been demonstrated. DBE improves SB disease management and can substitute for more complex investigations. Additional data will come to light in years to come. Combining DBE with CE, CT/MRI enteroclysis in a new era for SB work-up and treatment is the likely future.

Barriers to transition in young adults with neurogenic bladder.

INTRODUCTION: 'Transition' not only involves finding an adult healthcare provider, but also includes the process of developing the patient's ability to care for him/herself. Recent literature states that 40% of young adults with special healthcare needs are receiving the tools needed for transition. Pediatric urologists treating patients with complex anomalies, such as spina bifida, often anticipate poor outcomes for patients who are ill equipped for transition to adult care. The goal of this study was to identify potential barriers for young adults with neurogenic bladder when transitioning to independent care. STUDY DESIGN: A prospective IRB-approved study was performed on all patients with neurogenic bladder referred to the transitional urology clinic. Reasons for missed appointments were tracked, and all patients were asked to complete the Transition Readiness Assessment Questionnaire (TRAQ) in private prior to an appointment. The TRAQ responses are scaled 1-5, with higher numbers corresponding to higher transition readiness of each individual skill. The mean score for each question was calculated across all patients, and the mean TRAQ score was calculated across all questions for each patient. To assess if certain subgroups were more prepared for transition, mean scores were compared between sexes, patients aged <19 and ≥19 years old, and between ambulatory and full-time wheelchair users with unpaired t-tests. RESULTS: A total of 73% (58/79) of patients referred to the transitional clinic came to their appointment. The most common reason for missed clinic appointments was related to health insurance coverage (47%). A total of 42 patients completed the TRAQ at a mean age of 19.5 years old; 90% (38/42) had spina bifida. Females, ambulatory patients, and those ≥19 years old had higher overall mean TRAQ scores, but these differences were not statistically significant. The highest TRAQ scores were related to taking and ordering medications, utilization of medical supplies, communication with healthcare providers, and assisting with household duties. The majority of the patients indicated 'I am learning to do this'. The lowest scores were in response to questions about health insurance coverage, payments for medications or medical equipment, financial help, and utilization of community services. Most patients responded 'I do not know how but I want to learn'. CONCLUSIONS: Young adults with neurogenic bladder needed the most guidance during transition to independent care, with management of health insurance and finances. Based on these findings, dedicated social work and nurse visits have been included into the transition process.

The pharmacodynamics and activity of intranasally administered insulin in healthy male volunteers.

The objective of the study was to assess the bioavailability and absorption dynamics of intranasal insulin (with di-decanoyl-alpha-phosphatidylcholine, DDPC, as absorption enhancer) in two potencies (U200 and U500). Toward this aim, the euglycemic clamp technique combined with somatostatin (100 micrograms/h) was used. Insulin was administered to 12 healthy males: 5 IU intravenously (20-min infusion); 10 IU subcutaneously; 50 IU (U200) and 50 IU, 100 IU, and 150 IU (U500) intranasally. Peak insulin levels (mean +/- SD) were reached at 17.9 +/- 2.6, 77.9 +/- 38.3, 23.3 +/- 5.4, 25.4 +/- 8.4, 26.2 +/- 8.3, and 27.5 +/- 5.8 min, respectively. For the 50 IU dose, peak glucose requirements during the clamp and time to peak were not significantly different for U200 and U500: 548.8 +/- 279.5 vs. 452.4 +/- 232.9 mg/min and 41.3 +/- 16.2 vs. 51.5 +/- 29.9 min, respectively. Compared with intravenous insulin, the bioavailability calculated from the total area under the insulin curve was 13.2% (95% confidence interval 7.9, 21.9) and 8.8% (95% confidence interval 5.6, 13.8), and compared with subcutaneous insulin, the bioavailability was 14.8% (95% confidence interval 8.7, 25.2) and 9.9% (95% confidence interval 6.4, 15.4) for the U200 and U500 preparations, respectively. An apparent nonlinear dose-dependent relation was found for the U500 potency. The within-subject variability of the areas under the curves of plasma insulin after the administration of 100 IU was 43.6% (range 20.7-85.7). In conclusion, this nasal insulin preparation has promising absorption and action profiles in both potencies, which makes it suitable for further exploration of clinical applications.

Metabolic efficacy of preprandial administration of Lys(B28), Pro(B29) human insulin analog in IDDM patients. A comparison with human regular insulin during a three-meal test period.

OBJECTIVE: The objective of this study was to compare the efficacy of the rapid-acting Lys(B28), Pro(B29) human insulin analog, insulin lispro, with currently available short-acting human insulin in a multiple injection therapy (MIT) regimen with respect to blood glucose and plasma insulin profiles and to serum metabolites (lactate, free fatty acids, glycerol, and beta-hydroxybutyrate) in 12 well-controlled type 1 diabetic subjects (8 male, HbA1c 6.8 +/- 0.9% [mean +/- SD]). RESEARCH DESIGN AND METHODS: After a run-in period of 4 weeks, patients were treated with either lispro at mealtime or human insulin 30 min before the meal for two periods of 4 weeks in a randomized open-label crossover study. Intermediate-acting insulin (NPH insulin) was given at bedtime. At the end of both study periods, metabolic profiles were assessed from 10:00 P.M. to 7:00 P.M. the next day. RESULTS: During the treatment periods, glycemic control was stable during lispro but improved during human insulin (delta HbA1c lispro 0.1 +/- 0.48, NS; human insulin -0.41 +/- 0.34%, P < 0.05). Glucose excursions, as measured by the incremental AUC, during the day and for the 2-h postprandial periods, were lower, although not significantly, for lispro. Insulin profiles demonstrated a faster rise after administration of lispro as compared with human insulin, peaking at 61 +/- 11.9 and 111 +/- 48.1 min (P < 0.01). Glycerol levels showed a slight increase before lunch and dinner, suggestive of enhanced lipolytic activity and compatible with the lower insulin levels. CONCLUSIONS: Lispro insulin applied in an MIT regimen creates more physiologic insulin profiles and tends to lower the glycemic excursions during the day compared with short-acting insulin. The analog can be applied safely in an MIT regimen, with mealtime intervals up to 5 h.

Incidental biliary adenofibroma with dysplastic features.

We present a case of an incidentally detected cystic liver mass on CT scan, with histology showing biliary epithelium embedded in fibrous stroma and dysplastic features, consistent with an adenofibroma. This is only the third case described in the literature with malignant histology and the first case with angiographic imaging and subsequent management with preoperative embolization prior to surgical resection. We discuss the differential of the imaging findings and the features of this rare entity. Because of the risk of malignant transformation, consideration of this tumour is important to ensure early detection and ultimately resection for improved survival.

Preventing complications in celiac disease: our experience with managing adult celiac disease.

Celiac disease is, as we know it, rather than being a rare and incurable disease until the 1950's, both quite common in screening studies and readily treatable. Three conditions are triggered by gluten consumption: celiac disease, the skin rash dermatitis herpetiformis and gluten ataxia. We describe our follow up for out clinic management, as evidence based data about such an approach are lacking in current literature. No food, beverages or medications containing any amount of gluten can be taken. Compliance is often difficult especially when patients are asymptomatic. We control a cohort, in daily practice, of over 700 adult patients. The majority of patients manage the diet without any problems. We describe our follow up in general, for serology, laboratory and histology. Forty percent of our newly diagnosed celiac patients do have a BMI over 25 kg/m(2). An appropriate attitude for this problem is lacking. The problem of slowly weaning off Dapsone over 5-10 years in DH is recognized. The bone density is checked in all newly diagnosed celiac patients. We control, if necessary, by telephone and lab controls done in local cities and see our patients only every two years face-to-face for follow up. The main question is if the adherence to a GFD, quality of life and prevention of complications is improved by visiting a dedicated celiac clinic. We hope to standardize this attitude on evidence data in the years to come.

Reconstruction of the symphysis pubis to repair a complex midline hernia in the setting of congenital bladder exstrophy.

PURPOSE: A 40-year-old man with congenital midline defect and wide pubic symphysis diastasis secondary to bladder exstrophy presented with a massive incisional hernia resulting from complications of multiple prior abdominal repairs. Using a multi-disciplinary team of general, plastic, and urologic surgeons, we performed a complex hernia repair including creation of a pubic symphysis with rib graft for inferior fixation of mesh. METHODS: The skin graft overlying the peritoneum was excised, and the posterior rectus sheath mobilized, then re-approximated. The previously augmented bladder and urethra were mobilized into the pelvis, after which a rib graft was constructed from the 7th rib and used to create a symphysis pubis using a mortise joint. This rib graft was used to fix the inferior portion of a 20 × 25 cm porcine xenograft mesh in a retro-rectus position. With the defect closed, prior skin scars were excised and the wound closed over multiple drains. RESULTS: The patient tolerated the procedure well. His post-operative course was complicated by a vesico-cutaneous fistula and associated urinary tract and wound infections. This resolved by drainage with a urethral catheter and bilateral percutaneous nephrostomies. The patient has subsequently healed well with an intact hernia repair. The increased intra-abdominal pressure from his intact abdominal wall has been associated with increased stress urinary incontinence. CONCLUSIONS: Although a difficult operation prone to serious complications, reconstruction of the symphysis pubis is an effective means for creating an inferior border to affix mesh in complex hernia repairs associated with bladder exstrophy.

Non-absorbable sutures are associated with lower recurrence rates in laparoscopic percutaneous inguinal hernia ligation.

INTRODUCTION: Laparoscopic hernia repair with percutaneous ligation of the patent processes vaginalis is a minimally invasive alternative to open inguinal herniorrhaphy in children. With the camera port concealed at the umbilicus, this technique offers an excellent cosmetic result. It is also faster than the traditional laparoscopic repair with no differences in complication rates or hospital stay. The goal of this study was to describe a series of consecutive patients, emphasizing the impact of suture materials (absorbable vs. non-absorbable) on hernia recurrences. METHODS: A retrospective review was performed of consecutive transperitoneal laparoscopic subcutaneous ligations of a symptomatic hernia and/or communicating hydrocele by 4 surgeons. Patients > Tanner 2 or with prior hernia repair were excluded. The success of the procedure and number of sutures used was compared between cases performed with absorbable vs. non-absorbable suture. Risk factors for surgical failure (age, weight, number of sutures used, suture type) were assessed with logistic regression. RESULTS: 94 patients underwent laparoscopic percutaneous hernia ligation at a mean age of 4.9 years. Outcomes in 85 (90%) patients with 97 hernia repairs at a mean of 8 months after surgery revealed 26% polyglactin vs 4% polyester recurrences (p = 0.004) which occurred at mean of 3.6 months after surgery, Table 1. Repairs performed with non-absorbable suture required only 1 suture more often than those performed with absorbable suture (76% vs 60%, p = 0.163). Logistic regression revealed suture type was an independent predictor for failure (p = 0.017). Weight (p = 0.249), age (p = 0.055), and number of sutures (p = 0.469) were not significantly associated with recurrent hernia. DISCUSSION: Our review of consecutive hernia repairs using the single port percutaneous ligation revealed a significantly higher recurrent hernia rate with absorbable (26%) versus non-absorbable (4%) suture. This finding remained significant in a logistic regression model irregardless of number of sutures placed, age, and weight. Though the authors acknowledge the drawback of the potential for learning curve to confound our data, we still feel these findings are clinically important as this analysis of outcomes has changed our surgical practice as now all providers involved perform this procedure with exclusively non-absorbable suture. We thus suggest that surgeons who perform this technique, especially those newly adopting it, use non-absorbable suture for optimal patient outcomes. CONCLUSIONS: Recurrent hernia after laparoscopic percutaneous hernia ligation was significantly lower in repairs performed with non-absorbable suture. Based on this data, we recommend the use of non-absorbable suture during laparoscopic ligation of inguinal hernias in children.

A model for multiparametric mri tissue characterization in experimental cerebral ischemia with histological validation in rat: part 1.

BACKGROUND AND PURPOSE: After stroke, brain tissue undergoes time-dependent heterogeneous histopathological change. These tissue alterations have MRI characteristics that allow segmentation of ischemic from nonischemic tissue. Moreover, MRI segmentation generates different zones within the lesion that may reflect heterogeneity of tissue damage. METHODS: A vector tissue signature model is presented that uses multiparametric MRI for segmentation and characterization of tissue. An objective (unsupervised) computer segmentation algorithm was incorporated into this model with the use of a modified version of the Iterative Self-Organizing Data Analysis Technique (ISODATA). The ability of the model to characterize ischemic tissue after permanent middle cerebral ischemia occlusion in the rat was tested. Multiparametric ISODATA measurements of the ischemic tissue were compared with quantitative histological characterization of the tissue from 4 hours to 1 week after stroke. RESULTS: The ISODATA segmentation of tissue identified a gradation of cerebral tissue damage at all time points after stroke. The histological scoring of ischemic tissue from 4 hours to 1 week after stroke on all the animals was significantly correlated with ISODATA segmentation (r=0.78, P<0.001; n=20) when a multiparametric (T2-, T1-, diffusion-weighted imaging) data set was used, less correlated (r=0.70, P<0.01; n=20) when a T2- and T1-weighted data set was used, and not correlated (r=-0.12, P>0.47; n=20) when only a diffusion-weighted imaging data set was used. CONCLUSIONS: Our data indicate that an integrated set of MRI parameters can distinguish and stage ischemic tissue damage in an objective manner.

Multiparametric MRI tissue characterization in clinical stroke with correlation to clinical outcome: part 2.

BACKGROUND AND PURPOSE: Multiparametric MRI generates different zones within the lesion that may reflect heterogeneity of tissue damage in cerebral ischemia. This study presents the application of a novel model of tissue characterization based on an angular separation between tissues obtained with the use of an objective (unsupervised) computer segmentation algorithm implementing a modified version of the Iterative Self-Organizing Data Analysis Technique (ISODATA). We test the utility of this model to identify ischemic tissue in clinical stroke. METHODS: MR parameters diffusion-, T2-, and T1-weighted imaging (DWI, T2WI, and T1WI, respectively) were obtained from 10 patients at 3 time points (30 studies) after stroke: acute (

Zinc nutritional status during pregnancy: a longitudinal study.

Dietary zinc (Zn) intake and selected biochemical indices of Zn status were studied longitudinally at monthly intervals in 46 pregnant middle-income women, 10 of whom received a daily supplement of 15 mg Zn. Mean dietary Zn intake for the nonsupplemented subjects (group A) was 11.3 +/- 4.1 mg/day (56% of the Recommended Dietary Allowances), and for the Zn-supplemented subjects (group B) was 21.7 mg/day (109% of the Recommended Dietary Allowance), including an average intake of 11.1 mg/day as supplemental Zn. The mean plasma Zn concentration of group A at 2 months gestation, 71.4 +/- 9.8 micrograms/dl, was 17% lower than that of nonpregnant control women, and continued to decline significantly (p less than 0.01) between 2 and 10 months gestation. Plasma Zn of group B did not differ significantly from group A at any stage of gestation. Mean serum alkaline phosphatase activity of group B was higher than that of group A at 7 of 8 months studied (p less than 0.05). The level of prenatal iron supplementation in group A was negatively correlated with alkaline phosphatase activity and plasma Zn in the 2nd and 3rd trimesters, respectively. It is concluded that an early and progressive decline in plasma Zn which is not influenced by Zn intake occurs during gestation. Tentative standards for lower limits of normal at monthly intervals have been suggested. The higher alkaline phosphatase activity of group B compared with group A suggested that the dietary Zn intake of the latter was suboptimal. Prenatal supplemental iron may adversely affect maternal Zn status.